Abstract

Histoplasmosis causes life-threatening disseminated infection in adult patients living with untreated HIV. Although disease incidence has declined dramatically in countries with access to antiretroviral therapy, histoplasmosis remains prevalent in many resource-limited regions. A high index of suspicion for histoplasmosis should be maintained in the setting of a febrile multisystem illness in severely immunosuppressed patients, particularly in persons with hemophagocytic lymphohistiocytosis. Preferred treatment regimens for initial therapy include liposomal amphotericin B for severe disease, or itraconazole for mild to moderate disease. Subsequently, itraconazole maintenance therapy should be administered for at least one year and then discontinued if CD4 count increases to ≥150 cells/µL. Antiretroviral therapy, which improves outcome when administered together with an antifungal agent, should be instituted immediately, as the risk of triggering Immune Reconstitution Syndrome is low. The major risk factor for relapsed infection is nonadherence. Itraconazole prophylaxis reduces risk for histoplasmosis in patients with CD4 counts <100/µL but is not associated with survival benefit and is primarily reserved for use in outbreaks. Although most patients with histoplasmosis have not had recognized high-risk exposures, avoidance of contact with bird or bat guano or inhalation of aerosolized soil in endemic regions may reduce risk. Adherence to effective antiretroviral therapy is the most important strategy for reducing the incidence of life-threatening histoplasmosis.

Highlights

  • Histoplasma capsulatum, the most common endemic fungus in the United States [1], causes life-threatening disseminated disease in immunosuppressed patients living with HIV infection [2,3,4]

  • Treatment guidelines for histoplasmosis have been published by multiple organizations: the Infectious Diseases Society of America (IDSA), the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) in collaboration with the HIV Medical Association (HIVMA) and the IDSA; the American Thoracic Society; and the World Health Organization (WHO)/Pan American Health Organization (PAHO) [46,67,68,69]

  • Given that receipt of trimethoprim sulfamethoxazole (TMP/SMX), which has in vitro activity against H. capsulatum, was associated with lower disease incidence in the case control study [72], and that patients with Pneumocystis infection, which presumably was treated with TMP/SMX, in French Guiana had a lower incidence of histoplasmosis [73], it is plausible that TMP/SMX could reduce risk for histoplasmosis; further investigation will be necessary to assess this hypothesis

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Summary

Introduction

Histoplasma capsulatum, the most common endemic fungus in the United States [1], causes life-threatening disseminated disease in immunosuppressed patients living with HIV infection [2,3,4]. Histoplasmosis remains a threat to persons living with HIV in developed countries who either lack access to ART or are nonadherent [7]. This review will address the pathophysiology, clinical manifestations, and prevalence of histoplasmosis in adults living with HIV; describe the experience with various treatment regimens and discuss the antifungal regimens currently recommended by guidelines from public health agencies and professional societies; discuss the management of histoplasmosis in the setting of immune reconstitution; and review the recognized risk factors for histoplasmosis and strategies for disease prevention

Pathophysiology
Clinical Manifestations
Prevalence
Treatment
Alternative Regimens
Treatment Guidelines
Risk for Histoplasmosis
10. Prophylaxis
11. Non-Pharmacologic Strategies for Prevention
Findings
12. Conclusions
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